Mechanism of senescence-associated microRNA inhibiting cell growth and metastasis
Project/Area Number |
23300363
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Clinical oncology
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Research Institution | Hiroshima University |
Principal Investigator |
TAHARA Hidetoshi 広島大学, 大学院医歯薬保健学研究院, 教授 (00271065)
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Co-Investigator(Kenkyū-buntansha) |
OCHIYA Takahiro 国立がん研究センター研究所, 分子細胞治療研究分野, 分野長 (60192530)
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Project Period (FY) |
2011-04-01 – 2014-03-31
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
Keywords | 細胞老化 / がん / マイクロRNA / 核酸医薬 / miRNA / 癌細胞 / SIRT1 |
Research Abstract |
We identified that senescent associated miRNA, SA-miRNA, miR-22 is down-regulated in various cancer cell lines including MCF-7, MDA-MB-231 and SiHa cells, suggesting that miR-22 should play important roles for cancer progression. Transfection of miR-22 strongly induces cellular senescence accompanied by enlarged morphology, senescent-associated b-Gal activity (SA-b-Gal) and senescent associated heterochromatin foci (SAHF) formation. By using 3-UTR luciferase assay and Western analysis, we identified CDK6, SP-1, SIRT1 and Histone H3.3 are targets of miR-22. Furthermore, synthetic miR-22 delivery significantly suppresses tumor growth and metastasis in vivo in a murine breast metastasis cancer model using MDA-MB-231 Luc cell lines. Our study provides the first evidence that the senescence-associated miRNA induces cellular senescence in human fibroblasts and cancer cells, and acts as tumor suppressor to play an important role in tumorigenesis.
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Report
(4 results)
Research Products
(67 results)
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[Journal Article] Human telomerase reverse transcriptase and glucose-regulated protein 78 increase the life span of articular chondrocytes and their repair potential2012
Author(s)
Sato, M., Shin-ya, K., Lee, J.I., Ishihara, M., Nagai, T., Kaneshiro, N., Mitani, G., Tahara, H. & Mochida, J
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Journal Title
BMC Musculoskelet Disorders
Volume: 13
Issue: 1
Pages: 1-10
DOI
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Peer Reviewed
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[Presentation] The potential of senescence-associated miRNAs as tumor suppressor2011
Author(s)
Saori Fukunaga, Dan Xu, Fumitaka Takeshita, Yumiko Hino, Yasusei Kudo, Aya Tamaki, Erika Ishihara, Junko Matsunaga, Ryou-u Takahashi, Takashi Takata, Akira Shimamoto, Takahiro Ochiya, Hidetoshi Tahara
Organizer
第34回日本分子生物学会年会
Place of Presentation
パシフィコ横浜
Year and Date
2011-12-14
Related Report
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[Presentation] 細胞老化を調節する新規老化関連マイクロRNAの探索と機能解析2011
Author(s)
福永早央里, 徐丹, 竹下文隆, 日野由美子, 工藤保誠, 玉置彩, 石原えりか, 松永純子, 高橋陵宇, 高田隆, 嶋本顕, 落谷孝広, 田原栄俊
Organizer
第3回日本RNAi研究会
Place of Presentation
グランドプリンスホテル広島
Year and Date
2011-08-26
Related Report
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